Predicting clinical progression trajectories of early Alzheimer's disease patients
Viswanath Devanarayan, Yuanqing Ye, Arnaud Charil, Erica Andreozzi, Pallavi Sachdev, Daniel A. Llano, Lü Tian, Liang Zhu, Harald Hampel, Lynn D. Kramer, Shobha Dhadda, Michael C. Irizarry, for the Alzheimer's Disease Neuroimaging Initiative (ADNI)
Abstract
BACKGROUND: Models for forecasting individual clinical progression trajectories in early Alzheimer's disease (AD) are needed for optimizing clinical studies and patient monitoring. METHODS: Prediction models were constructed using a clinical trial training cohort (TC; n = 934) via a gradient boosting algorithm and then evaluated in two validation cohorts (VC 1, n = 235; VC 2, n = 421). Model inputs included baseline clinical features (cognitive function assessments, APOE ε4 status, and demographics) and brain magnetic resonance imaging (MRI) measures. RESULTS: to 0.29 in VC 1, which employed the same preprocessing pipeline as the TC. Utilizing these model-based predictions for clinical trial enrichment reduced the required sample size by 20% to 49%. DISCUSSION: Our validated prediction models enable baseline prediction of clinical progression trajectories in early AD, benefiting clinical trial enrichment and various applications.